Paracetamol iv as a single analgesic is very safe analgesic, but only for mild and moderate pain. It can be combined with many analgesic or adjuvan drugs to provide strong analgesic for postoperative pain. So, it can be the basic regiment for Multimodal Analgesia. Because of its safety it can be the choice for high risk surgical patient

1. Paracetamol iv as a Safety
Analgesic
A. Husni Tanra
Department of Anesthesiology IC and Pain
Management
Faculty of Medicine Hasanuddin University
Makassar

2. Pain Control
Opioid Non Opioid
NSAIDs Paracetamol
Now, almost all pain control managed with Multimodal Analgesia
Using Combination of Opioid with Non-Opioid Drugs

3. 1. Opioids
• Originally derived from poppies
• Body possesses endogenous
opioids
– enkephalins
– endorphins
• Opiate Receptors
– mu ()
– delta ()
– kappa ()
– sigma ()
• Opioid is a srong analgesic
• Opioids don’t damage organ.
Papaver somniferum
Ref. 2,5

4. Pharmacology of Opioids
• 1: inhibit transmission of pain
• 2: respiratory depression, euphoria,
constipation, physical dependence
• : inhibit transmission of pain
• : inhibit transmission of pain
• : autonomic effects, dysphoria,
hallucinations
Ref. 5

5. Sensory nerve terminal
Secondary neurons
Afferent neurons
Mechanism of Opioids: How it works?
Substance Ｐ
gultamatesMinami et al：OPIOID, pp.20-32, Kasseido, Tokyo (2005)
Stimulation
NMDA
receptor
NK1
receptor
Pain stimuli
μ-opioid
receptor
Opioids
Releasing transmitter substances
Activate
inhibitory nerve
μ-opioid
receptor
OPIOIDS
Inhibits excitationPain

6. Side Effect of Opioids
Common Side Effect
1. Nausea and
vomiting
2. Sedation
3. Urticaria
4. Constipation
Very rare/ almost none
1. Tolerance
2. Respiratory
depression
3. Dependence
4. Addiction
These side effects are dose related

7. Conclusions of opioids
• Opioid is strong or very strong
analgesic
• Safe to our organs
• But they have many annoying side
effects
Limited used as single drug

8. Non-Opioid Medications
• “Ceiling effect” to
analgesia
• Do not produce
constipation, tolerance
or physical dependence
• Most work by inhibiting
prostaglandin formation
• Mild to moderate analgesic
Ref. 1

9. 2. NSAID
TXA2
PGE2
PGI2 PGI2
Mechanism of Cox-1, 1971
Invention of Cox-2, 1999
All NSAIDs have similar evicacy

10. NSAIDs (nonselective inhibitor)
• Efficacy is similar amongst NSAIDs
• Differences in potency, time of onset,
& duration of action
• Side effects:
–GI bleeding
–renal dysfunction
–platelet dysfunction
Ref. 1,3

11. COX-1 vs Cox-2 Selective Inhibitor
(COXIB)
Selective COX-2 more safety than Non-
selective COX inhibitor
But, it still had disadvantages such as :
Cardiovascular Problem

12. Ibuprofen
Ketoprofen
Diclofenac
Meloxicam
Nimesulide
Celecoxib
Rofecoxib
Valdecoxib
Acetosal
Ketorolac
Indomethacin
Piroxicam
non-
selective
COX
inhibitor
preferentially
COX-2
selective
inhibitor
COX-2
selective
inhibitor
COX-1
selective
inhibitor
preferentially
COX-1
selective
inhibitor
COXIB
analgesic
anti-inflammatory
Less GI side effects, but more CVA
More GI side effects
Cox-1 vs Cox-2 selective inhibitor

13. Side effects of Opioid vs NSAID
Opioids ＮＳＡＩＤｓ
Side effects Nausea /Vomiting GI tract ulcer
Constipation Renal dysfunction
Sedation ( Titration) Liver dysfunction
Pruritis Asprine asthma
Respiratory depression
(very rare)
Coagulopathy (in some
drugs)
13

14. 3. Paracetamol iv
NEW but OLD DRUG
Acetominophen/PAAP
Route of Administration
 Orally
 Rectally
 Intravenously  available in Indonesia since 2009
Bertolini A, et al CNS Drugs reviews, 2006;12:250-275

15. Safety of paracetamol
1. All Age - Infant - Children
2. All Age – Elderly
3. Pregnant and Lactating Woman
4. Incidence of adverse effects
comparable to placebo
5. Renal Impairment
6. Mild Hepatic Impairment
Paracetamol As Single Analgesic Drugs

16. Safe for all age (infant to elderly)
1. Infant – Children
- For Mild Pain
- Similar to NSAIDs
- Adjunct to other treatments for more severe pain
- Useful in day care surgery (20-40 mg/kg), include
tonsillectomy
Paracetamol As Single Analgesic Drugs

17. Safe for all age (infant to elderly)
2. Elderly
- Paracetamol is preferred non opioid analgesic for older people
- No Need to Reduce the Dose of Paracetamol
Paracetamol As Single Analgesic Drugs

18. Safe for pregnant and lactating woman
3. During Pregnancy and Breastfeeding
- Analgesic of choice during pregnancy
- Prostaglandin actions may have adverse effects in woman
Slight increase in asthma in infants
- Safe for the treatment of migraine in mother who are
breastfeeding
Paracetamol As Single Analgesic Drugs

19. 3. Safe for pregnant and lactating woman
During Pregnancy and Breastfeeding
- Effective for Perineal pain during the first 24 hours
after birth
- Modestly effective in treating uterine pain
Paracetamol As Single Analgesic Drugs

20. 4. Incidence of adverse effects comparable to
placebo
Paracetamol As Single Analgesic Drugs

21. Hepatic impairment
- Safety in patients with liver disease
- Preferred than NSAIDs
- Need to reduce the dose for patient with significant degree of hepatic
impairment
- Cautions in patients who had depleted glutahione store (Cirrhosis, hepatitis
C, HIV, malnourished)
Interactions with warfarin
- Increase INR
Paracetamol As Single Analgesic Drugs
5. Safe in Mild Hepatic Impairment

22. Effective for Mild To Moderate Pain
Post Dental
Surgery
Post Orthopedic
Surgery
Post
Tonsillectomy
Post
Adenoidectomy
Post Inguinal
Surgery
Acute Pain
Associated with
Pharyngitis
Migraine
TTH (Tension-
type headache)
Paracetamol As Single Analgesic Drugs

23. Combination of Opiod
with Paracetamol
Opioid
Paracetamol
- Effective in Moderate to
Severe Pain
- Reduce Opioid Dose
- Reduce Opioid Side
effects
- Little Paracetamol Side
Efffects
-

24. PARACETAMOL , NSAIDS & COXIBS
Guidelines line for postoperative pain management
state that:
“Unless contraindication, all patients
should receive an around-the clock (ATC)
regiment on NSAIDs, COXIBs, or
Paracetamol”.
American Society of Anesthesiologists Task Force on Acute Pain Management
2004;100:1573-1581

25. Hyllested M, Jones S, Pedersen JL et al (2002) Comparative effect of paracetamol, NSAIDs or their combination in
postoperative pain management: a qualitative review. Br J Anaesth 88(2): 199–214.
Paracetamol can be the best alternative to
NSAID especially for high risk patients
It is appropriate to administer paracetamol with
NSAID, or COXIBs  additive or synergistic effects
Intravenous form of paracetamol has more
predictable onset and duration of actions
Qualitative Review of Paracetamol
and NSAIDs

26. 1.Sindet-Pedersen S.1997. Data on file.
* I.V. paracetamol was administered as a bio-equivalent dose of propacetamol.
Fast onset of action *
1
Sindet-Pedersen S, 1997
Rapid onset: 5min
Peak at ideal time: 30min
IV paracetamol for dental
Good residual effect at >6hrs

27. Qualitative Systemic Review 2010
Paracetamol and NSAIDs
Current evidence suggests that combination of
Paracetamol and an NSAIDs may offer superior
analgesia compared with either drug alone
(Anesth Analg 2010)

28. Combination of paracetamol and parecoxib may useful in patients
who are susceptible to hemorrhagic complications of NSAIDs
Parecoxib and Acetominophen

29. Paracetamol and Gabapentin
but
more episodes of nausea and vomiting and higher levels of sedation

30. Paracetamol and Local
Anesthetic Infiltrations

31. +
Parenteral
Analgesia
(iv paracetamol +
NSAIDsorCOX-2)
+
Regional
spinal/epidural
and/or
nerveblock
PainIntensity
Severe
Mild
T I M E

32. Opiate
And
NSAID
and
Paracetamol
Oral route available – give orally
Oral route unavailable –
Rectal paracetamol & NSAID Opiate: High
Tech: PCA
Low tech: IM algorithm Epidural infusion
analgesia
NSAID
and
Paracetamol
ParacetamolPain decreases
as time passes

33. Take Home Message
1. Paracetamol iv as a single analgesic is very
safe analgesic, but only for mild and
moderate pain.
2. It can be combined with many analgesic or
adjuvan drugs to provide strong analgesic for
postoperative pain.
3. So, it can be the basic regiment for
Multimodal Analgesia.
4. Because of its safety it can be the choice for
high risk surgical patient